Strategies for Aortic Root Measurement in Patients Undergoing Surveillance for Thoracic Aortic Disease

Journal of Clinical Medicine · 2026-04-28

Objectives: Several measurement techniques have been proposed to address the non-circular geometry of the aortic root. The Laplace diameter metric incorporates the cloverleaf anatomy of the aortic root and is derived via measurement of sinus-to-commissure lengths with subsequent doubling of the largest radius from the center. This study compares the conventional sinus-to-sinus with the novel Laplace method for sizing the aortic root and quantifying its implication on surgical decision-making. Methods: Patients undergoing surveillance at a high-volume aortic center were categorized by aortic root morphology as nondilated, non-syndromic dilated, bicuspid aortic valve and Marfan syndrome. Aortic root diameters by sinus-to-sinus and Laplace diameter methods were measured on computed tomography, compared using paired t-tests, and correlated using Spearman rank coefficients. Results: Of the 1297 patients assessed, 530 were included in the final analysis (nondilated n = 113, non-syndromic dilated n = 347, bicuspid aortic valve n = 50, Marfan syndrome n = 17). Aortic root diameters were significantly larger by Laplace than sinus-to-sinus diameter across all groups (sinus-to-sinus: 1.9 ± 5.5 mm; Laplace: 44.9 ± 7.0 mm; 95% confidence interval 2.72–3.34; p < 0.0001). Although Laplace and sinus-to-sinus diameter were correlated (Spearman r = 0.6789, 95% CI 0.6–0.7; p < 0.0001), the relationship was non-linear (R2 = 0.492). Laplace diameter increased the proportion of patients meeting surgical thresholds (2022 AHA/ACC guidelines) versus sinus-to-sinus: nondilated 0% vs. 1.77%, non-syndromic dilated 4.9% vs. 25.1%, bicuspid aortic valve 10.0% vs. 26.0%, and Marfan syndrome 23.5% vs. 52.9%. Conclusions: On average, Laplace diameter exceeded sinus-to-sinus diameter by 3 mm and would extend surgical eligibility to an additional 21% of patients under current guidelines.

Leveraging in-silico deep learning and computational analyses to predict the pathogenicity of ROBO4 variants of uncertain significance in aortic aneurysm and dissection patients

BMC Cardiovascular Disorders · 2026-02-04

Variants of uncertain significance (VUS) in genes implicated in thoracic aortic aneurysm (TAA) present clinical challenges due to ambiguous pathogenicity and low patient representation. This study investigates the pathogenic potential of missense VUS in the ROBO4 gene, previously associated with vascular integrity and ascending aortic aneurysm. Clinical and genetic data from five patients with heterozygous ROBO4 VUS and thoracic aortic aneurysms or dissections were analyzed. Computational tools including AlphaFold2, AlphaMissense, REVEL, PolyPhen-2, SIFT, FATHMM, MutationTaster2, GranthamMatrix, and PhastCons were utilized to predict pathogenicity and structural impacts. Patients exhibited varying severities of aortic pathology, from elective aneurysm repairs to extensive familial aneurysmal histories. Structural modeling revealed significant differences in residue positions and biochemical properties, particularly for extracellular domain variants affecting critical beta-sheet structures involved in vascular stability. Notably, patient-specific predictions aligned computational evidence with clinical severity, suggesting potential genotype-phenotype correlations. For example, a variant (Q44P) showed strong pathogenic predictions coinciding with severe familial presentations. These computational predictions, validated by clinical data, highlight a novel and efficient workflow for evaluating VUS pathogenicity, informing precision medicine, and guiding counseling for aortic degenerative diseases. Ultimately, we demonstrate the value of integrating computational modeling with clinical data to decipher the pathogenic significance of genetic variants in cardiovascular diseases.

Spectrum of Non-Invasive Biomarkers for Acute Cellular Rejection Surveillance in Heart Transplantation

Journal of Cellular Immunology · 2026-03-14

Objective: Heart transplantation remains the definitive treatment for patients with advanced heart failure, but post-transplant complications such as acute cellular rejection (ACR) continue to limit long-term outcomes. The current standard for ACR surveillance is endomyocardial biopsy, which is invasive and associated with procedural risks, variability in interpretation, high healthcare utilization costs, and poor patient tolerability. For these reasons, there is increasing interest in identifying non-invasive biomarkers that can reliably detect ACR. This review details the range of non-invasive methods for detecting ACR and to provide practical guidance for clinicians considering a transition to less invasive monitoring protocols following heart transplantation. Methods: We conducted a narrative review of published literature focusing on non-invasive biomarkers for ACR in heart transplantation. We specifically focused on evaluating donor-derived cell-free DNA, gene expression profiling, plasma microRNA, metabolomics, cytokines and chemokines, and extracellular vesicle approaches, with emphasis on clinical applicability, diagnostic performance, and limitations. Results: Our review identified several promising non-invasive biomarkers for ACR detection, with donor-derived cell-free DNA and gene expression profiling showing the most advanced clinical integration. Emerging approaches such as microRNA profiling, metabolomics, cytokine or chemokine panels, and extracellular vesicle analysis demonstrate potential in early-phase studies but require further validation. Most biomarkers exhibited high negative predictive value, though sensitivity and positive predictive values remained variable across platforms along with their applications in the early perioperative and late follow-up periods. None of the biomarker platforms distinguish ACR from antibody mediated rejection. Practical challenges including cost, assay standardization, and limited availability continue to impact widespread adoption. Conclusion: Non-invasive blood-based biomarkers show promise for improving acute cellular rejection surveillance in heart transplant recipients. While markers such as dd-cfDNA, extracellular vesicles, and microRNAs have demonstrated encouraging early results, their clinical use remains limited by variable inadequate sensitivity, low positive predictive value, inability to distinguish ACR from AMR, and lack of standardization. Ongoing investigations are expected to refine their diagnostic performance and guide their integration into routine clinical care.

Use of Inverse Probability Weighting in Cardiovascular Surgical Outcomes Research: Principles, Limitations, and Recommendations

European Journal of Cardio-Thoracic Surgery · 2026-03-07

This statistical primer presents a comprehensive introduction to the use of inverse probability of treatment weighting (IPTW), a method for rebalancing group confounders at baseline in cardiovascular surgical outcomes research. We leveraged a retrospective study comparing the outcomes of 2 different surgical approaches to aortic arch pathology to illustrate the essential aspects of performing IPTW, including basic theories, application, extreme weights, underestimated variance, heterogeneity of treatment effect, and multicollinearity. The limitations of IPTW were discussed with examples of solutions. Ten practical recommendations are made on avoiding the pitfalls in the use of IPTW. Proper use of IPTW may effectively reduce confounding bias by balancing confounders between different groups at baseline, retain a relatively large sample size, and allow for integration with other statistical methods. However, it is crucial to be fully aware of its limitations and carefully select appropriate methods to avoid improper use and data misinterpretation in cardiovascular outcomes research.

Increased medial collagen enhances aortic resilience against mural delamination from hydraulic fracturing

bioRxiv (Cold Spring Harbor Laboratory) · 2026-05-15

Abstract The aorta, normally resilient to hemodynamic stresses, becomes vulnerable to structural failure due to diverse conditions that weaken the wall. We injected fluid into excised specimens of human ascending aorta with pressure monitoring to quantify the impact of clinical and histological factors on mural damage. Two modes of medial injury emerged with distinct pressure tracings. Extravasation was characterized by diffuse infiltration of fluid with widespread damage of smooth muscle cells and collagen fibers but limited separation of elastic lamellae. By contrast, delamination was characterized by marked separation of elastic lamellae along a single plane with damage to cells and fibrillar matrix restricted to adjacent laminae. Aging, aortic dilatation, and family history associated with lower pressures causing delamination, whereas a diagnosis of hypertension associated with higher pressures suggesting resilience to dissection. Collagen fraction adjacent to delamination correlated with higher pressures as did decreased smooth muscle cell density and increased glycosaminoglycan fraction, although several clinical and histological variables were interrelated. Protein cross-linking strengthened and enzymatic digestion of collagen weakened the aortic wall, while acute cell lysis with detergent had no effect. We conclude that increased functional medial collagen has an adaptive protective role in aortic remodeling rather than signifying medial degeneration.

Management of Thoracic Aortic Infections

Contemporary cardiology · 2026-01-01

AortaPlot: A Modular End-to-End Protocol for Automated Aortic Imaging Analysis, Visualization, and Standardized Clinical Reporting to Support Aortic Surveillance

medRxiv · 2026-01-11

Abstract Background: Quantitative assessment of aortic morphology from computed tomography (CT) underpins diagnosis, surveillance, and risk stratification in aortic disease. However, existing analysis workflows are often fragmented, algorithm-specific, and limited to discrete vessel segments, constraining reproducibility, longitudinal comparison, and integration of emerging computational methods. The objective of this study was to describe AortaPlot, a modular, end-to-end computational framework designed to standardize continuous aortic quantification and generate anatomically contextualized outputs suitable for clinical interpretation, as well as downstream machine learning and longitudinal modeling. Methods: AortaPlot ingests CT imaging data and performs three-dimensional aortic segmentation using a replaceable segmentation engine. A continuous vascular centerline is computed from the aortic root to the aortic bifurcation and parameterized by arc length. Orthogonal cross-sectional planes are resampled at configurable intervals, and vessel diameter is quantified using a geometry-adaptive Sliding Axis algorithm that identifies the maximum orthogonal diameter independent of cross-sectional shape. Twenty anatomical landmarks are automatically detected and embedded within the measurement framework. The system generates landmark-annotated diameter-versus-length profiles, high-resolution regional analyses, standardized radiomic feature sets, annotated full length aortic visualization and fixed-view multi-angle 3D surface visualizations. Results: Across representative normal and pathological cases, AortaPlot reproducibly reconstructed full-length centerlines and generated anatomically ordered, landmark-annotated diameter profiles spanning the entire aorta. Continuous profiling captured physiologic tapering as well as focal aneurysmal dilation, while region-specific oversampling enabled detailed characterization of localized pathology. Outputs are compiled into standardized, surgeon-oriented reports integrating continuous quantitative profiles, focused segment analysis, anatomically contextualized radiomic features, landmark measurements, annotated aortic visualization and six-view 3D visualizations with fixed rotational spacing. Conclusions: AortaPlot establishes a reproducible, extensible framework for continuous aortic morphology analysis that unifies segmentation, measurement, anatomical context, and visualization within a single pipeline. By standardizing representation across the full vessel length and across time, this protocol reduces analytic variability and produces structured outputs directly amenable to radiomics, machine learning, and longitudinal modeling, providing a scalable foundation for reproducible aortic surveillance and future AI-driven risk stratification.

Healthcare burden of mixed aortic valve stenosis and insufficiency disease

Journal of Medical Economics · 2026-03-09

OBJECTIVE: To compare mortality, healthcare utilization, and costs between patients with symptomatic and asymptomatic mixed aortic valve disease (MAVD). METHODS: We analyzed Optum United Health Care database for US patients with aortic insufficiency (AI) claims (2017-2024) and prior/concurrent aortic stenosis (AS) claims, requiring 12 months continuous enrollment. Patients with baseline aortic valve replacement (AVR) were excluded. Symptomatic MAVD (SMAVD) was defined as ≥2 baseline visits for heart failure, angina, dyspnea, or syncope. Outcomes included mortality, time to home health/skilled nursing facility (SNF), and annualized healthcare utilization and costs, analyzed using Cox proportional hazard and general linear models. RESULTS: = 97,448) were symptomatic at diagnosis. Of initially asymptomatic patients, 58.94% became symptomatic within 5 years. Only 22% received AVR within 5 years. SMAVD patients had higher mortality (HR 1.48, 95% CI 1.44-1.53), home health utilization (HR 1.32, 95% CI 1.30-1.35), SNF admissions (HR 1.38, 95% CI 1.35-1.41), and $11,120 higher annual costs. CONCLUSIONS: SMAVD patients experience significantly worse outcomes than asymptomatic patients. Early detection and timely interventions are critical to reducing MAVD's healthcare burden.

Circulating T cell specific extracellular vesicles as biomarkers of acute cellular rejection after lung transplantation

American Journal of Transplantation · 2026-04-01

T cell counts, as well as, T cell sEV RNA cargoes (Cd3, Cd8, Ifng, Tcrb, and microRNA (Mir)21a) were significantly upregulated in mice receiving allogeneic compared to syngeneic lungs at the postoperative day 7 time point. Second, translating these findings to clinical lung transplantation, we analyzed circulating T cell sEV RNA cargoes with time-matched surveillance transbronchial allograft biopsies in 20 patients. In eight patients with >A1 ACR, eight candidate RNA biomarkers (CD8, TCR, IFNG, HLA-DRA, CD38, MIR21, MIRLET7I, MIR101) were significantly upregulated compared to 12 patients without ACR. Collectively, these findings support further investigation of T cell sEVs as a novel biomarker for ACR diagnosis in lung transplantation.

Clinical, Physiologic, and Anatomic Outcomes of a Novel Bioprosthetic Aortic Valved Conduit

Journal of Clinical Medicine · 2026-04-30

Background: In 2020, the first pre-assembled bioprosthetic aortic valved conduit (AVC) was approved in the United States. This study compares its anatomic and functional outcomes to traditional hand-sewn composite conduits in patients undergoing aortic root replacement. Methods: This retrospective study compared 118 patients receiving the pre-assembled AVC (2021–2023) versus 66 patients with hand-sewn conduits (2012–2020) after elective bio-Bentall procedures. Primary outcomes were post-operative mortality and complication rates. Secondary outcomes included anatomic and hemodynamic changes. Graft dimensions were obtained from post-operative computed tomography (CT). Echocardiographic parameters were collected at early and late follow-up. Between-group differences and longitudinal changes were assessed using linear mixed-effects models. Results: Groups were comparable in age (pre-assembled 63 ± 11 vs. hand-sewn 64 ± 11 years) and predominantly male. Despite significantly higher concomitant hemiarch rates in pre-assembled conduits (91.5% vs. 28.8%, p < 0.001), 30-day mortality, stroke, and reoperation for bleeding were comparable between groups. Pre-assembled conduits demonstrated superior hemodynamics with lower baseline peak gradients (Δ 9.1 mmHg, p < 0.001), lower mean gradients (Δ 5.3 mmHg, p < 0.001), and larger indexed effective orifice area (Δ 0.27 cm2/m2, p = 0.018). Annual rates of hemodynamic and dimensional change were minimal and comparable between groups. Kaplan–Meier analysis showed no survival difference at 3 years. Conclusions: The pre-assembled AVC demonstrates equivalent safety and superior early hemodynamic performance compared to hand-sewn conduits, with stable mid-term anatomic and functional outcomes.